The accumulation of a specific protein in the aging brain may be the cause of numerous devastating neurodegenerative diseases – most notably Alzheimer’s disease.

But it’s not amyloids – the proteins that most health experts blame for the brain-wasting condition. It’s an entirely new culprit.

In a groundbreaking study from Stanford University School of Medicine, researchers detailed the significance of a protein called C1q, which was previously known as the initiator of the immune system response. After analyzing brain tissue in mice of varying ages, as well as postmortem samples of a 2-month-old infant and an elderly person, they discovered that C1q exponentially increases in the aging brain – creating as much as a 300-fold buildup. Comparatively, most age-associated increases of proteins in the brain are only three- or four-fold.

The research team revealed that as the brain ages, C1q accumulates around the brain’s synapses – contact points that connect the brain’s nerve cells to one another. Rather than being naturally cleared by the brain, the C1q sticks, making these synapses vulnerable to destruction from the brain’s immune cells.

According to study author Dr. Ben Barres, the findings could fundamentally change the way scientists and doctors perceive neurodegenerative diseases, as well as lead to treatments that could alleviate the devastating effects of age-related brain disorders. Classic symptoms of neurodegneration range anywhere from severe memory loss to problems with motor function and complete loss of limb movement.

“We’re suggesting the reason the old brain is so vulnerable to Alzheimer’s disease is because of this massive buildup of C1q,” Barres, professor and chair of neurobiology at Stanford, told FoxNews.com. “One of the things that’s very interesting about this pattern is that the earliest accumulation of C1q starts in regions of the brain that are well-known to be most vulnerable to neurodegenerative disease – the hippocampus and substantia nigra.”

The complement system

C1q is a well-established component of what is known as the complement system – a group of 20 proteins that help antibodies and macrophages clear pathogens from the body. Considered the initiator of the system, C1q is responsible for recognizing the body’s “garbage,” such as bacteria, dying cells, and other harmful agents.

After locating these potentially dangerous cells, C1q binds to them and triggers a molecular reaction known as the amplifying cascade, in which the remaining 19 complement proteins bind to and coat the debris. This allows the macrophages (immune cells) to recognize the complement-tagged junk and eliminate it from the body.

“In the body, this system makes a lot of sense,” Barres said. “All the cells in the body contain inhibitors to the complement, so normal cells aren’t targeted and destroyed. For example, a normal liver cell will be fine, so it doesn’t have to worry about showers of complement protein.”

It was previously thought that the complement system did not exist in the brain, but in 2007, Barres’ group discovered that this system is actually hard at work in the brains of infants. As a young brain grows, it generates an excess of synapses that will potentially form new neural circuits. However, since too many synapses are created, the brain had to develop a mechanism for eliminating the ones deemed unnecessary.

“The mystery was nobody knew how the extra synapses were removed,” Barres explained.

Through their research, they found that this synaptic pruning was done by the complement system. The microglia – the brain’s version of immune cells – were secreting C1q, while other brain cells called astrocytes were responsible for secreting the rest of the complement proteins. As a result, the microglia would then attack the complement coated synapses, eliminating the excess from the brain.

“This is what really got us interested,” Barres said. “Neurodegenerative disorders are well described as unwanted synapse degeneration. So there is massive synapse loss, but no one knows why. We thought maybe the complement system is way overactive in Alzheimer’s. It’s not normally active in the typical adult brain, but in Alzheimer’s, it turns on like a switch.”

Complement gone wrong

Barres explained that when the complement system gets reactivated in the aging brain, an overabundance of C1q is created by the microglia, while the other complement proteins are somehow not activated. The C1q then targets the synapses but does not get cleared from the brain, so the protein remains on the neural connectors – causing more and more damage.

Barres’ explanation for this is that the synapses in the aging brain are different from those in the developing brain.

“We infer the existence of aging synapses that aren’t present in young brains – what we call senescent synapses,” Barres said. “We don’t know why they become this way. We infer that the old synapses are changing with age. One of the things about the brain that makes it different from most other tissues is the cells don’t turnover. The neurons you’re born with you’ll have your entire life.”

It’s possible that the senescent synapses become “sticky,” Barres theorized, which allows for this accumulation of C1q. This leaves the synapses on the brink of catastrophe, since a traumatic brain event such as a trauma or a stroke could trigger an activation of the remaining complement proteins, leading to massive synapse destruction.

According to Barres, his findings stand in contrast to current ways of thinking, as most scientists believe the pathology of Alzheimer’s begins with the buildup of amyloid plaque, which causes the loss of brain synapses and subsequent inflammation. Instead, he believes the amyloid buildup is a symptom of the disease rather than the cause.

“We think people have the ordering backwards,” Barres said. “We believe the complement turns on first and starts to kill synapses. If that’s true, the implication is we just need to block this complement cascade to treat Alzheimer’s.”

Barres is so confident about his findings that he is already developing a drug to target the complement system in the brain. In 2011, he co-founded a company, Annexon, which has been working on creating a drug that binds and inhibits the C1q protein. While their main focus has been on alleviating the effects of Alzheimer’s, Barres said this kind of drug could potentially help those suffering from a full range of neurodegenerative disease.

“One thing is clear is that the compliment mechanism is activated very highly in all neurodegenerative diseases – Parkinson’s, multiple sclerosis, Alzheimer’s, Huntington’s, etc.,” Barres said. “If we can block this pathway, we should be able to block the neurodegeneration process in many, many people.”